Estrogen Promotes Mandibular Condylar Fibrocartilage Chondrogenesis and Inhibits Degeneration via Estrogen Receptor Alpha in Female Mice

Temporomandibular joint degenerative disease (TMJ-DD) is a chronic form of TMJ disorder that specifically afflicts people over the age of 40 and targets women at a higher rate than men. Prevalence of TMJ-DD in this population suggests that estrogen loss plays a role in the disease pathogenesis. Thus, the goal of the present study was to determine the role of estrogen on chondrogenesis and homeostasis via estrogen receptor alpha (ERα) during growth and maturity of the joint. Young and mature WT and ERαKO female mice were subjected to ovariectomy procedures and then given placebo or estradiol treatment. The effect of estrogen via ERα on fibrocartilage morphology, matrix production, and protease activity was assessed. In the young mice, estrogen via ERα promoted mandibular condylar fibrocartilage chondrogenesis partly by inhibiting the canonical Wnt signaling pathway through upregulation of sclerostin (Sost). In the mature mice, protease activity was partly inhibited with estrogen treatment via the upregulation and activity of protease inhibitor 15 (Pi15) and alpha-2- macroglobulin (A2m). The results from this work provide a mechanistic understanding of estradiol on TMJ growth and homeostasis and can be utilized for development of therapeutic targets to promote regeneration and inhibit degeneration of the mandibular condylar fibrocartilage.National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Numbers R56DE020097 (SW) and F32DE026366 (JR

Ewing Sarcoma Protein Ewsr1 Maintains Mitotic Integrity and Proneural Cell Survival in the Zebrafish Embryo

BACKGROUND:The Ewing sarcoma breakpoint region 1 gene (EWSR1), also known as EWS, is fused to a number of different partner genes as a result of chromosomal translocation in diverse sarcomas. Despite the involvement of EWSR1 in these diverse sarcomas, the in vivo function of wild type EWSR1 remains unclear. PRINCIPAL FINDINGS:We identified two zebrafish EWSR1 orthologues, ewsr1a and ewsr1b, and demonstrate that both genes are expressed maternally, and are expressed ubiquitously throughout zebrafish embryonic development. Morpholino induced knockdown of both zebrafish ewsr1 genes led to mitotic defects with multipolar or otherwise abnormal mitotic spindles starting from the bud stage (10 hour post-fertilization (hpf)). The abnormalities in mitotic spindles were followed by p53-mediated apoptosis in the developing central nervous system (CNS) leading to a reduction in the number of proneural cells, disorganization of neuronal networks, and embryonic lethality by 5 days post-fertilization. siRNA silencing of EWSR1 in Hela cells resulted in mitotic defects accompanied by apoptotic cell death, indicating that the role of EWSR1 is conserved between zebrafish and human. CONCLUSIONS:Ewsr1 maintains mitotic integrity and proneural cell survival in early zebrafish development

Non-cationic proteins are associated with HIV neutralizing activity in genital secretions of female sex workers.

CAPRISA, 2015.Abstract available in pdf

Can obtaining informed consent alter self-reported drinking behaviour? A methodological experiment.

BACKGROUND: Informed consent is the foundation of the ethical conduct of health research. Obtaining informed consent may unwittingly interfere with the data collected in research studies, particularly if they concern sensitive behaviours that participants are requested to report on. To address gaps in evidence on such research participation effects, we conducted a methodological experiment evaluating the impact of the informed consent procedure on participants' reporting behaviour, specifically on their self-report of drinking behaviour as measured by Alcohol Use Disorder Identification Test (AUDIT). METHODS: A two arm double blinded randomised controlled trial was used. University students present in London student unions at the time of recruitment were contacted in two phases (an initial run-in phase followed by the main phase). Those providing positive responses to verbal questions: 1) "are you a student?"; 2) "do you drink alcohol?"; 3) "would you like to take part in a brief health survey, which will take around 5 minutes?" were recruited. Participants received one of the two envelopes by chance, with the sequence generated by an online random sequence generator. One contained the participant information sheet, informed consent form and the AUDIT questionnaire (the intervention group), while the other contained only the AUDIT questionnaire (the comparator group). The primary outcome was the mean AUDIT score, which ranges from 0 to 40. The secondary outcome was the proportion of participants in each group scoring 8 or more on the AUDIT, the threshold score for hazardous and harmful drinking warranting intervention. RESULTS: A total of 380 participants were successfully recruited, resulting in 190 participants in each group, of which 378 were included in the final analysis. There is no evidence of any statistically significant difference between groups in the primary outcome. A statistically significant difference in the secondary outcome was found in the run-in phase only, and not in the main phase, or overall. Moreover, between-group outcome differences between the two phases suggest an important influence of setting on reporting behaviour. CONCLUSIONS: There is no strong evidence that completion of informed consent itself alters self-reporting behaviour with regards to alcohol, though the effect of settings needs to be further studied

Guidelines for the Management of HIV Infection in Pregnant Women and the Prevention of Mother-to-Child Transmission of HIV

The prevalence of HIV infection amongst women giving birth in England and Wales has increased every year since 1990. Results from the Unlinked Anonymous Surveys of infection in pregnancy, show that in 2003, the prevalence reached one in 180 (0.56%) in inner London, one in 271 in outer London (0.37%) and one in 1,282 (0.08%) in the rest of England [1]. The majority of these women are from sub-Saharan Africa. The Department of Health policy of recommending an HIV test to every pregnant woman [2] has resulted in an increase in the proportion of these women who are aware of their diagnosis prior to delivery (more than 80% in London in 2001) and a decrease in the absolute number of infants infected in the UK [3]

Estabelecimento de valores de referências para subpopulações de linfócitos T em adultos e crianças no Brasil

In Brazil, the existing reference values for T-lymphocytes subsets are based on data originated in other countries. There is no local information on normal variation for these parameters in Brazilian adults and children. We evaluated the normal variation found in blood donors from five large Brazilian cities, in different regions, and in children living in Salvador, and Rio de Janeiro. All samples were processed by flow cytometry. The results were analyzed according to region, gender, and lifestyle of blood donors. A total of 641 adults (63% males), and 280 children (58% males) were involved in the study. The absolute CD3+, and CD4+ cells count were significantly higher for females (adults and children). Higher CD4+ cell count in adults was associated with smoking, while higher CD8+ count was found among female children. Higher counts, for all T-cells subsets, were detected in blood donors from southeast / south regions while those living in the northern region had the lowest values. Individuals from midwestern and northeastern regions had an intermediate count for all these cells subsets. However, these differences did not reach statistical significance. In Brazil, gender and smoking, were the main determinants of differences in T-lymphocytes reference values.Os valores de referências de linfócitos T existentes no Brasil são baseados em dados originados de outros países. Não existem dados locais da variação normal para estes parâmetros em adultos e crianças brasileiras. Avaliamos a variação normal encontrada em doadores de sangue de cinco grandes cidades brasileiras em diferentes regiões e em crianças residentes em Salvador e Rio de Janeiro. Todas as amostras foram processadas por citometria de fluxo. Os resultados foram analisados de acordo com região, gênero e estilo de vida dos doadores. Um total de 641 adultos (63% homens) e 280 crianças (58% meninos) participaram do estudo. Valores absolutos de CD3+ e CD4+ foram significantemente maiores no gênero feminino (adultos e crianças). Maiores valores de CD4+ em adultos foram associados com tabagismo, enquanto que maiores valores de CD8+ foram encontrados entre crianças do sexo feminino. Adultos das regiões sul e sudeste apresentaram maiores valores absolutos para todas as células T enquanto que adultos da região norte, apresentaram menores valores. Indivíduos residentes no nordeste e centro-oeste obtiveram contagens intermediárias para todas as populações de células T. Entretanto, estas diferenças entre as regiões, não demonstraram diferença estatística. No Brasil, gênero e tabagismo foram os principais determinantes para diferenças em valores de referências de linfócitos T